Chromosome studies

Chromosomes are the threadlike structures of DNA in every cell in our bodies that contain our genes. Cytogenetics is a word used to describe the study of chromosomes. The chromosomes need to be stained in order to see them with a microscope. When stained, the chromosomes look like strings with light and dark bands.

A picture (an actual photograph from one cell) of all 46 chromosomes, in their pairs, is called a karyotype. A normal female karyotype is written 46, XX, and a normal male karyotype is written 46, XY.

The standard analysis of the chromosomal material evaluates both the number and structure of the chromosomes, with an accuracy of over 99.9%. Chromosome analyses are usually done using a blood sample, prenatal specimen, skin biopsy, or other tissue sample. Chromosomes are analyzed by specially trained healthcare staff that have advanced degrees in cytogenetic technology and genetics.

Chromosome studies may be done when a child is born with multiple birth defects. Chromosome studies may also be done when people have certain types of leukemias and lymphomas, to look for specific changes in the order of the chromosome material linked with these types of cancers.

DNA studies

A gene is a section of DNA on a chromosome. The stretch of DNA is a code, or recipe, for making a specific protein the body needs to function properly. To study genes, you have to analyze the DNA to determine whether the DNA “alphabet” has any “spelling errors” in it. There are two ways to analyze the DNA:

Direct DNA studies

Direct DNA studies simply look directly at the gene in question for an error. This technology is called FISH or PCR. Errors in the DNA may include a replication of the gene’s DNA (duplication), a loss of a piece of the gene’s DNA (deletion), a change in a single unit (called a base pair) of the gene’s DNA (point mutation), or the repeated replication of a small sequence (for instance, 3 base pairs) of the gene’s DNA (trinucleotide repeat). Different types of errors or mutations are found in different disorders. It is usually very important to find the mutation that is present in a family by first studying the family member with the genetic disorder (in this case, cancer) before testing other relatives without the cancer. When a particular mutation is found in a relative with cancer, other family members can choose to have testing for the mutation to determine if they have an increased risk of developing certain cancers and passing the mutation on to the next generation. The DNA needed for direct DNA studies is usually obtained by taking a blood sample.

Indirect DNA studies

Sometimes, the gene that causes a condition (when mutated) has not yet been identified, but researchers know approximately where it lies on a particular chromosome. Or other times, the gene is identified, but direct gene studies are not possible because the gene is too large to analyze. In these cases, indirect DNA studies may be done. Indirect DNA studies involve using markers to find out whether a person has inherited the crucial region of the genetic code that is passing through the family with the disease. Markers are DNA sequences located close to or even within the gene of interest. Because the markers are so close, they are almost always inherited together with the disease. When markers are this close to a gene, they are said to be linked. If someone in a family has the same set of linked markers as the relative with the disease, this person often also has the disease-causing gene mutation. Because indirect DNA studies involve using linked markers, these types of studies are also called linkage studies.

Indirect studies usually involve blood samples from several family members, including those with and without the disorder in question. This is to establish what pattern of markers appear to be associated with the disease. Once the disease-associated pattern of markers is identified, it is possible to offer testing to relatives to determine who inherited this pattern and, as such, is at increased risk of cancer.

The accuracy of linkage studies depends on how close the markers are to the faulty gene. In some cases, a reliable marker is not available, and the test, therefore, cannot give any useful information to the healthy family members. In many cases, several family members are needed to establish the most accurate set of markers to determine who is at risk for the disease in the family. Linkage studies may take many weeks to complete because of the complexity of these studies.

Many of the cancer susceptibility genes that we know about today were discovered using linkage studies of families who had multiple family members with cancer.

Biochemical genetic studies

Biochemical genetic testing involves the study of enzymes in the body that may be abnormal in some way. Enzymes are proteins that regulate chemical reactions in the body. The enzymes may be deficient or absent, unstable, or have altered activity that can lead to signs in an adult or child (for example, birth defects). There are hundreds of enzyme defects that can be studied in humans. Sometimes, rather than studying the gene mutation that is causing the enzyme to be defective in the first place, it is easier to study the enzyme itself (the gene product). The approach depends on the disorder. Biochemical genetic studies may be done from a blood sample, urine sample, spinal fluid, or other tissue sample, depending on the disorder.

Protein truncation studies

Another way to look at gene products, rather than the gene itself, is through protein truncation studies. Testing involves looking at the protein a gene makes to see if it is shorter than normal. Sometimes a mutation in a gene causes it to make a protein that is truncated (shortened). With the protein truncation test, it is possible to “measure” the length of the protein the gene is making to see if it is the right size or shortened. Protein truncation studies can be performed on a blood sample. These types of studies are often performed for disorders in which the known mutations most often lead to shortened proteins.